Letermovir Injection and Neoral

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Using cycloSPORINE together with letermovir may increase the blood levels of both medications. Talk to your doctor if you have any questions or concerns. You may need a dose adjustment or more frequent monitoring to safely use both medications. Contact your doctor if your condition changes or you experience increased side effects such as nausea, vomiting, diarrhea, abdominal pain, dizziness, fatigue, headache, tremors, seizures, fever, sore throat, unusual bruising or bleeding, and increased or decreased urination. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

ADJUST DOSE: Coadministration with cyclosporine may significantly increase the plasma concentrations of letermovir. The proposed mechanism is cyclosporine inhibition of the OATP1B1-mediated hepatic uptake of letermovir. Cyclosporine exposure may also increase due to inhibition of CYP450 3A4-mediated metabolism by letermovir. According to the product labeling, letermovir peak plasma concentration (Cmax), systemic exposure (AUC) and concentration at 24 hours postdose (C24hr) increased by an average of 48%, 111% and 106%, respectively, when letermovir (240 mg orally once daily) was coadministered with cyclosporine (200 mg single oral dose). Cyclosporine Cmax, AUC and C24hr increased by an average of 8%, 66% and 119%, respectively, when a 50 mg single oral dose was coadministered with letermovir 240 mg orally once daily. In pharmacokinetic studies, median steady-state AUC of letermovir was 34,400 ng*hr/mL when dosed at 480 mg orally once daily without cyclosporine, compared to 60,800 ng*hr/mL when dosed at 240 mg orally once daily with cyclosporine. Likewise, a median value of 100,000 ng*hr/mL was reported when letermovir was given intravenously at 480 mg once daily without cyclosporine, compared to 70,300 ng*hr/mL when given intravenously at 240 mg once daily with cyclosporine. In hematopoietic stem cell transplant patients, the bioavailability of letermovir was 35% at a dosage of 480 mg orally once daily without cyclosporine, compared to 85% at a dosage of 240 mg orally once daily with cyclosporine.

MANAGEMENT: The dosage of letermovir should be decreased to 240 mg orally or intravenously once daily when coadministered with cyclosporine. If cyclosporine is initiated during letermovir prophylaxis therapy, letermovir dosage should be decreased to 240 mg once daily beginning with the next dose. If cyclosporine is discontinued, letermovir dosage should be increased to 480 mg once daily beginning with the next dose. No dosage adjustment of letermovir is needed if cyclosporine dosing is interrupted due to high cyclosporine levels. Cyclosporine whole blood concentrations should also be monitored frequently during treatment and after discontinuation of letermovir, and the dosage adjusted accordingly. In addition, clinicians should be aware that the magnitude of CYP450 3A- and OATP1B1/3-mediated drug interactions with coadministered drugs may be different when letermovir is used with cyclosporine. The combined effect of the two drugs on CYP450 3A may be similar to that of a strong CYP450 3A inhibitor, hence clinicians should refer to the prescribing information for dosing recommendations of the CYP450 3A substrate with a strong CYP450 3A inhibitor. Similarly, letermovir and cyclosporine may demonstrate some additive effects on OATP1B1 inhibition, although cyclosporine by itself is already a strong OATP1B1/3 inhibitor.

Letermovir Injection

Generic Name: letermovir

Brand name: Prevymis

Synonyms: Letermovir (oral/injection), Letermovir

What is Letermovir Injection?

Neoral

Generic Name: cyclosporine

Brand name: Gengraf, Neoral, Sandimmune, Sandimmune

Synonyms: Neoral (Capsules, Modified)

What is Neoral?